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AXL is an essential factor and therapeutic target for metastatic ovarian cancer

Erinn B Rankin1, Katherine C Fuh, Tiffany E Taylor

  • 1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Center for Clinical Sciences Research, Stanford University, Stanford, California 94305-5152, USA.

Cancer Research
|September 23, 2010
PubMed

Insights

Targeting the AXL receptor tyrosine kinase effectively inhibits metastatic ovarian cancer progression. This study validates AXL as a therapeutic target, showing AXL inhibition reduces invasion and tumor spread without toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • The receptor tyrosine kinase AXL is implicated in cancer metastasis.
  • Therapeutic strategies targeting AXL in metastatic disease are largely unexplored.
  • AXL expression is elevated in advanced ovarian tumors and metastases, but not normal ovarian tissue.

Purpose of the Study:

  • To investigate AXL as a therapeutic target for metastatic ovarian cancer.
  • To evaluate the efficacy of targeting the GAS6/AXL pathway in vivo.
  • To determine the potential of soluble AXL receptors as therapeutic agents.

Main Methods:

  • Genetic inhibition of AXL in human metastatic ovarian tumor cells.
  • In vivo studies in animal models of metastatic ovarian cancer.
  • Administration of soluble human AXL receptors to block the GAS6/AXL pathway.

Main Results:

  • Genetic AXL inhibition prevented metastatic disease initiation in vivo.
  • AXL inhibition decreased cancer cell invasion and matrix metalloproteinase activity.
  • Soluble AXL receptor blockade profoundly inhibited established metastatic ovarian cancer progression with no observed normal tissue toxicity.

Conclusions:

  • The GAS6/AXL pathway is genetically validated as a target for inhibiting metastatic tumor progression.
  • Soluble AXL receptors represent a promising therapeutic candidate for metastatic ovarian cancer.
  • Targeting AXL offers a novel strategy for treating ovarian cancer with limited effective therapies.

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